Dysfunctional Heteroreceptor Complexes as Novel Targets for the Treatment of Major Depressive and Anxiety Disorders
Abstract
:1. Introduction
2. Clinical Characteristics and Epidemiological Aspects Related to Depression and Anxiety
2.1. Major Depressive Disorder
2.2. Anxiety
2.3. Clinical Responses Associated to the Use of Pharmacological Compounds in Patients Suffering from Depression and Anxiety Disorders
3. Emergent Concepts of Receptor Heterodimerization and Their Impact on Nervous System Function
4. Receptor Homo and Heterodimerization with Relevance for MDD
4.1. Role of 5-HT Transporters and Receptor Systems in MDD
4.1.1. Role of 5-HT1AR-5-HT2AR Heteroreceptor Complexes in MDD
4.1.2. 5-HT1AR-FGFR1 Heteroreceptor Complex in MDD
4.1.3. 5-HT-Galanin Heterocomplexes in MDD
4.1.4. 5-HTR-OXTR Heterocomplexes in Depression
4.1.5. 5-HT1AR-D2LR Heterocomplexes in MDD
4.2. Influence of Other Heteroreceptor Complexes in MDD
4.2.1. Dopamine D1R-D2R Heterocomplexes in MDD
4.2.2. GalaninR2 (GalR2)-NPYY1R Heterocomplexes in MDD
4.2.3. OpioidR Heterocomplexes in MDD
5. Receptor-Receptor Interactions with Relevance for Anxiety
5.1. 5-HT1AR-5-HT2AR Isoreceptor Complexes in Anxiety
5.2. Opioid Heteroreceptor Complexes in Anxiety
5.3. Galanin Heteroreceptor Complexes in Anxiety
5.4. Gal-NPY Heteroreceptor Complex in Anxiety
5.5. Dopamine D1R-D2R Heterocomplexes in Anxiety
5.6. D2LR-5-HT1AR Heterocomplexes in Anxiety
5.7. D2R-OXTR Heterocomplexes in Anxiety
6. Ghrelin
6.1. Growth Hormone Secretagogue Receptor 1a (GHSR1a)-Containing Heteromer Complexes as Links between Stress-Induced Eating Behavior with Depression/Anxiety
6.2. GHSR1a-DA Receptor Heteroreceptor Complexes
6.3. GHSR1a-D1R Heteromers
6.4. GHSR1a-D2R Heteromers
7. Novel Therapeutic Strategies for Treatment of MDD and Anxiety Based on GPCR Heteroreceptor Complexes
Potential Allosteric Downstream-Mediated Receptor-Receptor Interactions in the Action of Fast Antidepressant Effects of Ketamine
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Treatment Strategies Related to Heteroreceptor Complexes | ||||
---|---|---|---|---|
Strategy | Outcome | Putative Heteroreceptor Examples | Disorder | Reference |
Selective protomer ligands | Induced oligomer formation | D2R-OXTR | Anxiety | [64] |
Gal1R-Gal2R-5-HT1AR | Depression and anxiety | [40,110,130,135,229,355] | ||
DOR-MOR | Depression, anxiety, and nociception | [205,206,207,208] | ||
A2AR-D2R | Parkinson’s disease and schizophrenia | [75,90,95,198,338,339,340,341] | ||
Biased ligands | Cross-talk effects between protomers | [103,334,335,356] | ||
Homo-/Hetero-receptor bivalent compounds | Facilitatory/inhibitory effects by binding on both protomeric recognition sites | KOR-MOR | Nociception | [351] |
MOR-mGluR5R | Nociception | [5] | ||
Disrupting homo/heteroreceptor peptides | Disruption of constitutive heteroreceptor complexes | D1R-D2R | Depression and anxiety | [183,184,200] |
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Pérez de la Mora, M.; Borroto-Escuela, D.O.; Crespo-Ramírez, M.; Rejón-Orantes, J.d.C.; Palacios-Lagunas, D.A.; Martínez-Mata, M.K.; Sánchez-Luna, D.; Tesoro-Cruz, E.; Fuxe, K. Dysfunctional Heteroreceptor Complexes as Novel Targets for the Treatment of Major Depressive and Anxiety Disorders. Cells 2022, 11, 1826. https://doi.org/10.3390/cells11111826
Pérez de la Mora M, Borroto-Escuela DO, Crespo-Ramírez M, Rejón-Orantes JdC, Palacios-Lagunas DA, Martínez-Mata MK, Sánchez-Luna D, Tesoro-Cruz E, Fuxe K. Dysfunctional Heteroreceptor Complexes as Novel Targets for the Treatment of Major Depressive and Anxiety Disorders. Cells. 2022; 11(11):1826. https://doi.org/10.3390/cells11111826
Chicago/Turabian StylePérez de la Mora, Miguel, Dasiel O. Borroto-Escuela, Minerva Crespo-Ramírez, José del Carmen Rejón-Orantes, Daniel Alejandro Palacios-Lagunas, Magda K. Martínez-Mata, Daniela Sánchez-Luna, Emiliano Tesoro-Cruz, and Kjell Fuxe. 2022. "Dysfunctional Heteroreceptor Complexes as Novel Targets for the Treatment of Major Depressive and Anxiety Disorders" Cells 11, no. 11: 1826. https://doi.org/10.3390/cells11111826